No

Antiarrhythmic Agent, Class I-B

Management of serious ventricular arrhythmias; suppression of PVCs

C

Hypersensitivity to mexiletine or any component; cardiogenic shock; second- or third-degree AV block (except in patients with a functioning artificial pacemaker)

Can be proarrhythmic. May cause acute hepatic injury. Use cautiously in patients with first-degree block, pre-existing sinus node dysfunction, intraventricular conduction delays, significant hepatic dysfunction, hypotension, or severe CHF. Electrolytes disturbances alter response. Alterations in urinary pH may change urinary excretion. Rare hepatic toxicity may occur. Electrolyte abnormalities should be corrected before initiating therapy (can worsen CHF).

>10%:

Central nervous system: Lightheadedness (10.5% to 25%), dizziness (20% to 25%), nervousness (5% to 10%), incoordination (10.2%)

Gastrointestinal: GI distress (41%), nausea/vomiting (40%)

Neuromuscular & skeletal: Trembling, unsteady gait, tremor (12.6%), ataxia (10% to 20%)

1% to 10%:

Cardiovascular: Chest pain (2.5% to 7.5%), premature ventricular contractions (1% to 2%), palpitations (4% to 8%), angina (1.7%), proarrhythmic (10% to 15% in patients with malignant arrhythmias)

Central nervous system: Confusion, headache, insomnia (5% to 7%), depression (2.4%)

Dermatologic: Rash (3.8% to 4.2%)

Gastrointestinal: Constipation or diarrhea (4% to 5%), xerostomia (2.8%), abdominal pain (1.2%)

Neuromuscular & skeletal: Weakness (5%), numbness of fingers or toes (2% to 4%), paresthesias (2.4%), arthralgias (1.4%)

Ocular: Blurred vision (5% to 7%), nystagmus (6%)

Otic: Tinnitus (2% to 2.5%)

Respiratory: Shortness of breath(3%)

<1% (Limited to important or life-threatening symptoms): Leukopenia, agranulocytosis, thrombocytopenia, positive antinuclear antibody, SLE syndrome, increased LFTs, diplopia, syncope, edema, hot flashes, hypertension, short-term memory loss, psychological changes, psychosis, convulsion, diaphoresis, urinary hesitancy, urinary retention, malaise, impotence, decreased libido, pharyngitis, dysphagia, esophageal ulceration, upper GI bleeding, increased transaminases, hepatitis, hepatic necrosis, exfoliative dermatitis, Stevens-Johnson syndrome, congestive heart failure (patients with pre-existing ventricular dysfunction), diaphoresis, salivary changes, alopecia, pancreatitis (rare), myelofibrosis (patients with pre-existing myeloid abnormalities), hypotension, sinus arrest, AV block, conduction disturbances, cardiogenic shock, torsade de pointes, hallucinations, seizures, peptic ulcer, drug-induced lupus-like syndrome

Case reports: Pulmonary fibrosis, urticaria

Has a narrow therapeutic index and severe toxicity may occur slightly above the therapeutic range, especially with other antiarrhythmic drugs; acute ingestion of twice the daily therapeutic dose is potentially life-threatening; symptoms of overdose includes sedation, confusion, coma, seizures, respiratory arrest and cardiac toxicity (sinus arrest, A-V block, asystole, and hypotension); the QRS and Q-T intervals are usually normal, although they may be prolonged after massive overdose; other effects include dizziness, paresthesias, tremor, ataxia, and GI disturbance.

Treatment is supportive, using conventional therapies (fluids, positioning, vasopressors, antiarrhythmics, anticonvulsants); sodium bicarbonate may reverse the QRS prolongation, bradyarrhythmias and hypotension; enhanced elimination with dialysis, hemoperfusion or repeat charcoal is not effective.

CYP2D6 enzyme substrate; CYP1A2 enzyme inhibitor

Quinidine may increase mexiletine blood levels.

Theophylline blood levels are increased by mexiletine.

Urinary alkalinizers (antacids, sodium bicarbonate, acetazolamide) may increase mexiletine blood levels.

Class IB antiarrhythmic, structurally related to lidocaine, which inhibits inward sodium current, decreases rate of rise of phase 0, increases effective refractory period/action potential duration ratio

Absorption: Elderly have a slightly slower rate of absorption but extent of absorption is the same as young adults

Distribution: V_d: 5-7 L/kg

Protein binding: 50% to 70%

Metabolism: Low first-pass metabolism

Half-life: Adults: 10-14 hours (average: 14.4 hours elderly, 12 hours in younger adults); increase in half-life with hepatic or heart failure

Time to peak: Peak levels attained in 2-3 hours

Elimination: 10% to 15% excreted unchanged in urine; urinary acidification increases excretion, alkalinization decreases excretion

Adults: Oral: Initial: 200 mg every 8 hours (may load with 400 mg if necessary); adjust dose every 2-3 days; usual dose: 200-300 mg every 8 hours; maximum dose: 1.2 g/day (some patients respond to every 12-hour dosing). Patients with hepatic impairment or CHF may require dose reduction. When switching from another antiarrhythmic, initiate a 200 mg dose 6-12 hours after stopping former agents, 3-6 hours after stopping procainamide.

Food may decrease the rate, but not the extent of oral absorption; diets which affect urine pH can increase or decrease excretion of mexiletine; avoid dietary changes that alter urine pH

Therapeutic range: 0.5-2 mg/mL; potentially toxic: >2 mg/mL

Abnormal liver function test, positive ANA, thrombocytopenia

Mexiletine has a very narrow therapeutic index and significant toxicity may occur slightly above the therapeutic range. This is particularly problematic when other antiarrhythmic drugs are also being administered. Symptoms of mexiletine excess include sedation, confusion, seizures, respiratory arrest, and cardiac toxicity (sinus arrest, AV block, asystole, hypotension). Note that the QRS and QT intervals are usually normal, although they may be prolonged after massive overdose. As with other antiarrhythmic agents, mexiletine is also proarrhythmic, particularly in patients with underlying cardiovascular disease and electrolyte abnormalities.

Dizziness and nervousness are common; may cause confusion and insomnia

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; barbiturates may decrease the effects of mexiletine; monitor

No information available to require special precautions

No effects or complications reported

Take exactly as directed, with food or antacids, around-the-clock. Do not take additional doses or discontinue without consulting prescriber. Do not change diet without consulting prescriber. You will need regular cardiac checkups and blood tests while taking this medication. You may experience drowsiness or dizziness, numbness, or visual changes (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, or heartburn (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or headaches or sleep disturbances (usually temporary, if persistent consult prescriber). Report chest pain, palpitation, or erratic heartbeat; increased weight or swelling of hands or feet; chills, fever, or persistent sore throat; numbness, weakness, trembling, or unsteady gait; blurred vision or ringing in ears; or difficulty breathing. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

Administer around-the-clock rather than 4 times/day, 3 times/day, etc, (ie, 12-6-12-6, not 9-1-5-9) to promote less variation in peak and trough serum levels

Capsule: 150 mg, 200 mg, 250 mg

Denaro CP and Benowitz NL, "Poisoning Due to Class 1B Antiarrhythmic Drugs. Lignocaine, Mexiletine, and Tocainide," Med Toxicol Adverse Drug Exp, 1989, 4(6):412-28.

Frank SE, Snyder JT, "Survival Following Severe Overdose With Mexiletine, Nifedipine, and Nitroglycerin," Am J Emerg Med, 1991, 9(1):43-6.

Kempton J, Manoukian A, Levine B, et al, "A Mexiletine Intoxication," J Anal Toxicol, 1994, 18(6):346-7.

Moak JP, Smith RT, and Garson A Jr, "Mexiletine: An Effective Antiarrhythmic Drug for Treatment of Ventricular Arrhythmias in Congenital Heart Disease," J Am Coll Cardiol, 1987, 10(4):824-9.

Nelson LS and Hoffman RS, "Mexiletine Overdose Producing Status Epilepticus Without Cardiovascular Abnormalities," J Toxicol Clin Toxicol, 1994, 32(6):731-6.